Bryophyllum pinnatum Inhibits Oxytocin and Vasopressin Signaling in Myometrial Cells.

The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT-C3, and cell lines expressing recombinant human OT and V1A receptors.We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT-C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V1A receptor-mediated signals with a similar potency (IC50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT-C3 cells.In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system.

How Physicians and Nursing Staff Perceive Effectiveness and Tolerability of Bryophyllum Preparations: An Online Survey in an Anthroposophic Hospital.

BACKGROUND: Bryophyllum preparations are widely used in anthroposophic medicine, most often for mental and behavioural disorders. Three prospective studies have revealed positive effects of Bryophyllum pinnatum on sleep quality, and various trials have shown very good tolerability. Results from animal models have indicated CNS depressant and anxiolytic effects. This survey was conducted at the hospital "Klinik Arlesheim" in Switzerland to find out how the physicians and the nursing staff perceive the effectiveness and the tolerability of the Bryophyllum preparations they most frequently use. DESIGN: Internal, anonymous online survey of healthcare professionals (April 8-May 31, 2022). The questionnaire comprised 105 multiple-choice questions. Answering the questions was taken as consent to participate in the survey. PARTICIPANTS AND METHODS: All physicians and nursing staff with a valid email address at the hospital "Klinik Arlesheim AG" were invited via email to participate in this REDCap survey. The data were analysed descriptively. RESULTS: Out of 266 invited participants, 48 answered some and 36 answered all questions (response rate between 18.0% and 13.5%). The participants had long experience with Bryophyllum preparations and were comprised approximately equal numbers of physicians and nursing staff. Various Bryophyllum preparations from the hospital's own production and Wala Heilmittel GmbH (in both cases produced from the species B. daigremontianum) and from Weleda AG (species B. pinnatum) were used. The indications for which most participants had prescribed or administered Bryophyllum preparations "very frequently" were anxiety, sleep disorders, crisis situations in oncology, posttraumatic stress disorder, benzodiazepine dependence/withdrawal, and depression. Improvements such as relief from restlessness, decreased anxiety, balance, easier falling asleep, better sleeping through, increased resilience, mood elevation, and less urge to move one's legs were reported "frequently" or "very frequently." Almost all participants agreed that Bryophyllum can be used to reduce the intake of synthetic sedatives or psychotropic drugs, but only approximately half believed that it could replace them. The majority of participants mentioned good tolerability of the various products, but a few reported occasional stomach or intestinal irritation, daytime fatigue, drowsiness, diarrhoea, and nausea. CONCLUSION: Bryophyllum preparations are perceived as helpful in the treatment of various mental disorders, particularly anxiety, and are generally well tolerated. Most of these preparations are used for indications that have not yet been clinically investigated.Bryophyllum-Präparate werden in der Anthroposophischen Medizin sehr häufig zur Behandlung von psychischen und Verhaltensstörungen eingesetzt. Drei prospektive Studien zeigten zudem positive Wirkungen von Bryophyllum pinnatum (BP) auf die Schlafqualität. Auch die Verträglichkeit wurde in allen bisherigen Studien als sehr gut bewertet. In Tiermodellen wurden ZNS-depressive und anxiolytische Effekte von BP festgestellt. Die hier durchgeführte Umfrage fand an der Klinik Arlesheim (Schweiz) statt. Sie diente dazu herauszufinden, wie Ärztinnen und Ärzte sowie das Pflegepersonal die Wirksamkeit und Verträglichkeit der von ihnen am häufigsten verwendeten Bryophyllum-Präparate wahrnehmen.Interne, anonyme, Online-Befragung unter ärztlichen und pflegerischen Fachkräften (8. April­31. Mai 2022). Der Fragebogen umfasste 105 Multiple-Choice-Fragen. Die Beantwortung der Fragen wurde als Zustimmung zur Teilnahme an der Umfrage interpretiert.Alle Ärztinnen, Ärzte und Pflegefachpersonen mit einer gültigen E-Mail-Adresse der "Klinik Arlesheim AG" wurden per E-Mail eingeladen, an dieser REDCap-Umfrage teilzunehmen. Die Daten wurden deskriptiv ausgewertet.Von den 266 eingeladenen Teilnehmenden beantworteten 48 einige und 36 alle Fragen (Antwortquote zwischen 18.0% und 13.5%). Die Teilnehmenden hatten langjährige Erfahrung mit Bryophyllum-Präparaten und setzten sich etwa zu gleichen Teilen aus ärztlichen und pflegerischen Fachkräften zusammen. Die Resultate zeigen, dass verschiedenste Bryophyllum-Präparate aus klinikeigener Herstellung, von der Wala Heilmittel GmbH (Art B. daigremontianum) und von der Weleda AG (Art B. pinnatum) verwendet werden. Zu den Indikationen, bei denen die meisten Teilnehmenden Bryophyllum-Präparate "sehr häufig" verordnet oder angewendet haben, gehören Angstzustände, Schlafstörungen, Krisensituationen in der Onkologie, Posttraumatische Belastungsstörung, Benzodiazepin-Abhängigkeit/Entzug und Depressionen. Gesundheitsverbesserungen wie Linderung von Unruhe, verminderte Angst, Ausgeglichenheit, leichteres Einschlafen, besseres Durchschlafen, erhöhte Belastbarkeit, Stimmungsaufhellung und weniger Drang, die Beine zu bewegen, wurden als "häufig" oder "sehr häufig" angegeben. Fast alle Teilnehmenden waren sich einig, dass Bryophyllum verwendet werden kann, um die Einnahme von synthetischen Beruhigungsmitteln oder Psychopharmaka zu reduzieren, aber nur etwa die Hälfte gab an, dass es diese ersetzen kann. Die Mehrheit der Teilnehmenden spricht von einer guten Verträglichkeit der verschiedenen Produkte. Einige wenige berichteten von gelegentlicher Magen- oder Darmreizung, Tagesmüdigkeit, Schläfrigkeit, Durchfall und Übelkeit.Bryophyllum-Präparate werden als hilfreich bei der Behandlung verschiedener psychischen Störungen, insbesondere bei Angstzuständen, angesehen und im Allgemeinen gut vertragen. Die meisten der angegebenen Präparate werden für Indikationen verwendet, die noch nicht klinisch untersucht worden sind.

Repurposing of Bryophyllum pinnatum for dysmenorrhea treatment: a systematic scoping review and case series.

Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of Bryophyllum pinnatum preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, in vivo, and in vitro studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of B. pinnatum are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a B. pinnatum product are described. The review revealed thirty-three experimental in vivo and in vitro studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of B. pinnatum extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of in vivo and in vitro data. The evidence reviewed therefore provided a rational basis for the use of B. pinnatum in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated B. pinnatum product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of B. pinnatum extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of B. pinnatum as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed.

Transplacental passage of hyperforin, hypericin, and valerenic acid.

Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John's wort and valerian are valid candidates, but safety data in pregnancy are lacking. The transplacental transport of hyperforin and hypericin (from St. John's wort), and valerenic acid (from valerian) was evaluated using the ex vivo cotyledon perfusion model (4 h perfusions, term placentae) and, in part, the in vitro Transwell assay with BeWo b30 cells. Antipyrine was used for comparison in both models. U(H)PLC-MS/MS bioanalytical methods were developed to quantify the compounds. Perfusion data obtained with term placentae showed that only minor amounts of hyperforin passed into the fetal circuit, while hypericin did not cross the placental barrier and valerenic acid equilibrated between the maternal and fetal compartments. None of the investigated compounds affected metabolic, functional, and histopathological parameters of the placenta during the perfusion experiments. Data from the Transwell model suggested that valerenic acid does not cross the placental cell layer. Taken together, our data suggest that throughout the pregnancy the potential fetal exposure to hypericin and hyperforin - but not to valerenic acid - is likely to be minimal.

Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John's wort.

Phytomedicines such as valerian and St. John's wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John's wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts.

Bryophyllum pinnatum and Improvement of Nocturia and Sleep Quality in Women: A Multicentre, Nonrandomised Prospective Trial.

Nocturia is a pathologic condition that significantly affects the quality of sleep. The aetiology of nocturia is multifactorial, and the evidence available on its management remains limited. Besides behavioural measures, validated pharmaceutical treatment options exist but are, however, associated with marked side effects. Prospective clinical studies with tablets prepared from the leaf press juice of the plant Bryophyllum pinnatum revealed a tendency towards reduction of micturition in patients with overactive bladder (OAB) and several improvements in sleep quality. These observations are in part supported by in vitro and in vivo data. In the present study, we investigated the effectiveness of Bryophyllum 50% chewable tablets in the treatment of nocturia and associated sleep disorders. Altogether, 49 women with idiopathic OAB and nocturia of ≥2 voids/night were treated with Bryophyllum 50% tablets for 3 weeks (350 mg chewable tablets, dosage 0-0-2-2 oral tablets; WELEDA AG, Arlesheim, Switzerland). Nocturia, voiding volumes at night (ml), quality of life, sleep quality, and daily sleepiness were assessed before and after treatment with a 3-day micturition diary, the International Consultation on Incontinence evaluating overactive bladder and related impact on quality of life (QoL) [ICIQ-OAB], the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS), respectively. The age of the study population was 68.5 ± 11.6 y. After treatment, nocturia diminished from 3.2 ± 1.4 to 2.3 ± 1.3 (P < 0.001) and the PSQI score decreased from 7.7 ± 3.7 to 6.6 ± 3.4 (P=0.004). Urgency, the ICIQ score, and the ESS lowered significantly, and the micturition volume showed a tendency to increase. No serious adverse drug reactions were reported, and compliance was good. The results show a beneficial effect on the nocturnal voids and sleep quality of women with OAB. Bryophyllum 50% tablets can be regarded as a well-tolerated alternative in the treatment of nocturia and broaden the repertoire of standard management.

Placental Passage of Protopine in an Ex Vivo Human Perfusion System.

The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. The study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.

Advanced in Vitro Safety Assessment of Herbal Medicines for the Treatment of Non-Psychotic Mental Disorders in Pregnancy.

When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs and resort to herbal medicines such as St. John's wort, California poppy, valerian, lavender, and hops. Nevertheless, these herbal medicines have not yet been officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, and inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we were previously able to show that extracts from these plants are likely to be safe at the usual clinical doses. In the present work, we wanted to extend our safety assessment of these herbal medicines by 1) looking for possible effects on gene expression and 2) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably lead to safety issues. Proteomics results were promising, as none of the five extracts significantly affected protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents of St. John's wort) and valtrate (typical for valerian) were the most obvious phytochemicals with respect to cytotoxic and apoptotic effects. A decrease in cell viability was evident with hypericin (≥1 µM) and valtrate (≥10 µM), whereas hyperforin (≥3 µM), hypericin (30 µM) and valtrate (≥10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound affected cell differentiation, except for hyperforin (≥1 µM), which had an inhibitory effect. This study suggests that extracts from St. John's wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. High plasma concentrations of some relevant compounds-hyperforin and hypericin from St. John's wort and valtrate from valerian-deserve special attention, however.

Medicinal Plants for the Treatment of Mental Diseases in Pregnancy: An In Vitro Safety Assessment.

Pregnancy is a critical period for medical care, during which the well-being of woman and fetus must be considered. This is particularly relevant in managing non-psychotic mental disorders since treatment with central nervous system-active drugs and untreated NMDs may have negative effects. Some well-known herbal preparations (phytopharmaceuticals), including St. John's wort, California poppy, valerian, lavender, and hops, possess antidepressant, sedative, anxiolytic, or antidepressant properties and could be used to treat mental diseases such as depression, restlessness, and anxiety in pregnancy. Our goal was to assess their safety in vitro, focusing on cytotoxicity, induction of apoptosis, genotoxicity, and effects on metabolic properties and differentiation in cells widely used as a placental cell model (BeWo b30 placenta choriocarcinoma cells). The lavender essential oil was inconspicuous in all experiments and showed no detrimental effects. At low-to-high concentrations, no extract markedly affected the chosen safety parameters. At an artificially high concentration of 100 µg/mL, extracts from St. John's wort, California poppy, valerian, and hops had minimal cytotoxic effects. None of the extracts resulted in genotoxic effects or altered glucose consumption or lactate production, nor did they induce or inhibit BeWo b30 cell differentiation. This study suggests that all tested preparations from St. John's wort, California poppy, valerian, lavender, and hops, in concentrations up to 30 µg/mL, do not possess any cytotoxic or genotoxic potential and do not compromise placental cell viability, metabolic activity, and differentiation. Empirical and clinical studies during pregnancy are needed to support these in vitro data.

Use of Herbal Medicines for the Treatment of Mild Mental Disorders and/or Symptoms During Pregnancy: A Cross-Sectional Survey.

Little is known about the treatment of mild mental disorders and/or symptoms (MDS) during pregnancy. Our main purpose was to compare the use of herbal medicines during pregnancy in women with and without MDS. A questionnaire consisting of 21 multiple-choice questions was distributed in the participating obstetrics clinics or birth centers in the Canton of Zurich, in Switzerland, from August 2018 to March 2019; 398 questionnaires were considered in the analysis. The use of any type of herbal medicines-including pharmaceutical herbal products as well as teas-during pregnancy was reported by 358 women (out of 398, 89.9%). Of these, 272 participants used pharmaceutical herbal products, whereby ginger (49.2%), raspberry leaf (42.7%), bryophyllum (37.8%), chamomile (27.2%), lavender (22%) and iron-rich herbs (12.3%) were the ones most commonly mentioned. More than half (207/398, 52.0%) of all participants reported suffering from MDS during pregnancy; only a few took (synthetic) psychoactive medications (5/398, 1.3%). The percentage of use of pharmaceutical herbal medicines was higher among women reporting MDS than among the remaining women (90.0 vs 75.9%; p < 0.001). At the same time, the prevalence of MDS was higher among users of pharmaceutical herbal products than among non-users (59.6 vs 34.0%; p = 0.001). Specific questions on candidate herbal medicines for the treatment of mild MDS revealed that bryophyllum (mentioned by 107 women), lavender (56 women) and valerian (20 women) were used to reduce stress, restlessness, sleep disorders and others, in part with perceived good to very good effectiveness and tolerability. The large majority of the pregnant women participating in the survey make use of herbal medicines. The particularly high prevalence of MDS among herbal medicine-users and the very rare use of synthetic psychoactive medications suggest that pregnant women rely on herbal medicines for treatment of mild MDS. The reported good effectiveness and tolerability of a few candidate herbal medicines deserve particular attention.

Placental Passage of Humulone and Protopine in an Ex Vivo Human Perfusion System.

The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.

Influence of Alternative Lifestyles on Antibiotic Use during Pregnancy, Lactation and in Children.

Alternative lifestyles are likely to be associated with distinct usage of specific medicinal products. Our goal was to find out whether the intake of antibiotics during pregnancy and by children differs according to whether the mothers have alternative or conventional lifestyles. Therefore, we investigated the use of antibiotics by pregnant women and by children up to 11 years of age participating in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother-infant pairs, one with alternative lifestyles (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 491) the other with conventional lifestyles (no selection based on lifestyle, n = 2343). Mothers in the alternative lifestyle group more frequently adhered to specific living rules and identified themselves with anthroposophy more than mothers in the conventional lifestyle group. The results revealed significant differences in antibiotic use during pregnancy and in children from 3 months to 10 years of age between the two groups. The rate of antibiotic use in children was consistently lower in the alternative lifestyle group than in the conventional lifestyle group. Antibiotic use in pregnancy was higher in low educated women, and maternal antibiotic use during lactation was higher after an instrumented delivery in hospital. Antibiotic use in the infant was higher when they had older sibs or were born in hospital, and lower in those who had been longer breastfed. After adjustment for these factors, the differences in antibiotic use between the alternative and conventional groups remained. The results suggest that an alternative lifestyle is associated with cautious antibiotic use during pregnancy, lactation and in children.

Bryophyllum pinnatum Compounds Inhibit Oxytocin-Induced Signaling Pathways in Human Myometrial Cells.

Bryophyllum pinnatum has been used in the treatment of premature labor, first in anthroposophic hospitals and, recently, in conventional settings as an add-on medication. In vitro work with hTERT human myometrial cells showed that B. pinnatum leaf press juice inhibits the increase of intracellular free calcium concentration induced by oxytocin, a hormone known to play a role in labor. Our aim was to identify fractions/compounds in B. pinnatum press juice that contribute to this inhibitory effect, and to investigate their effect on oxytocin-driven activation of the MAPK cascade. Several fractions/compounds from B. pinnatum press juice led to a concentration-dependent decrease of oxytocin-induced increase of intracellular free calcium concentration, but none of them was as strong as B. pinnatum press juice. However, the combination of a bufadienolide and a flavonoid-enriched fraction was as effective as B. pinnatum press juice, and their combination had a synergistic effect. B. pinnatum press juice inhibited oxytocin-driven activation of MAPKs SAPK/JNK and ERK1/2, an effect also exerted by the bufadienolide-enriched fraction. The effect of B. pinnatum press juice on oxytocin-induced signaling pathways was comparable to that of the oxytocin-receptor antagonist and tocolytic agent atosiban. Our findings further substantiate the use of B. pinnatum press juice preparations in the treatment of preterm labor.

Bryophyllum pinnatum in the treatment of restless legs syndrome: A case series documented with polysomnography.

Restless legs syndrome may seriously affect patients' sleep and quality of life, but established pharmacological therapy can often have severe side effects. Therefore, new therapeutic approaches such as well-tolerated preparations from the medicinal plant Bryophyllum pinnatum should be considered as alternatives. Their sedative and spasmolytic properties might contribute to improve patients' condition.

A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro.

Bryophyllum pinnatum has been used since the 1970s to prevent premature labour, first in anthroposophic hospitals and, more recently, also in the main Swiss perinatal centres. However, it is not known which compounds in B. pinnatum leaves contribute to the tocolytic effect. Here we studied the effects of a flavonoid-enriched fraction, the corresponding flavonoid aglycon mixture, a bufadienolide-enriched fraction, and B. pinnatum leaf press juice on human myometrial contractility in vitro. The strength (area under the curve and amplitude) and frequency of contractions were recorded using strips of human myometrium mounted in an organ bath system. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1 - 41 cell lines. Repeated addition of the flavonoid-enriched fraction, flavonoid aglycon mixture, bufadienolide-enriched fraction, or B. pinnatum leaf press juice led to a progressive decrease of contraction strength, without jeopardising the vitality of myometrium strips. The bufadienolide-enriched fraction was the most active, since 1 µg/mL of the bufadienolide-enriched fraction lowered the area under the curve to 40.1 ± 11.8% of the initial value, whereas 150 µg/mL of the flavonoid-enriched fraction, 6.2 µg/mL of the flavonoid aglycon mixture, and 10 µg/mL of the B. pinnatum leaf press juice were required to achieve comparable inhibition. A progressive increase of contraction frequency was observed, except in the case of the flavonoid aglycon mixture, which did not affect frequency. None of the test substances decreased myometrial cell viability, even at concentrations of 500 µg/mL of the flavonoid-enriched fraction, 40 µg/mL of the flavonoid aglycon mixture, 3.8 µg/mL of the bufadienolide-enriched fraction, and 75 µg/mL of the B. pinnatum leaf press juice, i.e., higher than those used in the myometrium experiments. Given the concentrations of flavonoids in the flavonoid-enriched fraction and B. pinnatum leaf press juice, and of bufadienolides in the bufadienolide-enriched fraction and B. pinnatum leaf press juice, it appears that bufadienolides may be mainly responsible for the relaxant effect.

Can Speech-Guided Breathing Influence Cardiovascular Regulation and Mood Perception in Hypertensive Patients?

OBJECTIVES: Anthroposophic therapeutic speech (ATS) has been shown to positively influence heart rate variability (HRV) and cardiorespiratory coordination in healthy volunteers. This prospective, exploratory, pre-post study was performed to investigate ATS effects on baroreflex sensitivity (BRS), heart rate (HR), HRV by standard deviation of beat to beat intervals (SDNN), blood pressure (BP), and mood in hypertensive patients. DESIGN: Patients received three ATS treatments, alternating with three sham interventions (control). During the sessions, BP and electrocardiography were continuously recorded. BRS and SDNN were analyzed from those measurements. Changes in mood score were assessed by a questionnaire. All data were compared before and after intervention (ATS and control). RESULTS: Thirty-one patients participated, the majority diagnosed with arterial hypertension (22 out of 31). Pre-post analysis of the data revealed immediate and significant changes in hypertensive patients during control and ATS with respect to BRS (control: 6.57 to 6.92 msec/mmHg, p = 0.0349; ATS: 6.03 to 7.27 msec/mmHg, p < 0.0001), SDNN (control: 39 to 42 msec, p = 0.0058; ATS: 38 to 43 msec, p = 0.0003), and HR (control: 74 to 71 beats per minute [bpm], p < 0.0001; ATS: 74 to 70 bpm, p < 0.0001). In normotensive patients, those changes were generally less pronounced and less significant with respect to BRS (control: 8.13 to 8.56 msec/mmHg, p = 0.1102; ATS: 8.20 to 8.98 msec/mmHg, p = 0.0273), SDNN (control: 36 to 40 msec, p = 0.0002; ATS: 35 to 38 msec, p = 0.0556), and HR (control: 80 to 77 bpm, p < 0.0001; ATS: 80 to 78 bpm, p < 0.0011). Only in hypertensive patients significant long-term changes were observed for BRS (6.6 to 7.7 msec/mmHg, p = 0.0070), SDNN (39.1 to 45.5 msec, p = 0.0074), and HR (75.8 to 67.2 bpm, p = 0.0001). No significant long-term changes were observed in normotensive patients. The mean systolic BP did not change significantly during this study. Both ATS and control also yielded improvements in the mood summary score, which again were more apparent for ATS than for sham interventions, but these were more pronounced among normotensive patients (3.5 to 4.2) than for hypertensive patients (2.9 to 3.9). CONCLUSION: The results indicate that ATS has the potential to improve cardiovascular parameters which play an important role in BP regulation capability.

Diet, medication use and drug intake during pregnancy: data from the consecutive Swiss Health Surveys of 2007 and 2012.

OBJECTIVE: The aim of this work was to gain knowledge on the health status of pregnant women in Switzerland, especially their attitude to and decisions about diet, use of medication and consumption of drugs, including alcohol and tobacco. METHODS: Data collected by the consecutive Swiss Health Surveys of 2007 and 2012 on sociodemographic and lifestyle characteristics (including nutrition), type and intake of medication, use of alcohol, tobacco and illicit drugs of the female population were analysed. To compare pregnant with non-pregnant women, a group of 10 times as many non-pregnant women (reference group, n = 3090) was matched with all the participating women who said they were pregnant at the time of the survey (pregnant group, n = 309). The two groups were then compared. RESULTS: The pregnant and non-pregnant participant groups were comparable with respect to most sociodemographic characteristics and both showed a high awareness of health-related issues. Significantly more pregnant than non-pregnant women revealed a high nutritional awareness, claiming to pay attention to what they ate (78.3 vs 73.0%). Frequent consumption of milk products and fish, and moderate consumption of meat were found more often in the pregnant group. Use of medication was comparable between the two groups, except that pregnant women took pain killers less frequently than did non-pregnant women (30.0 vs 61.5%) and relied more often on prescribed medication. Pregnant women were more restrictive in their alcohol consumption than non-pregnant women. Nevertheless, 10.0 and 1.9% of the pregnant women declared consumption of wine and beer, respectively, in the previous 7 days. Regular smoking was less frequent in the pregnant group than in the reference group (11.7 vs 30.3%) and less intensive (pregnant smokers smoked 3.6 cigarettes fewer per day). A few pregnant women (1.9%) said they consumed marijuana; no other illicit drugs were mentioned. CONCLUSIONS: In Switzerland, women of child-bearing age revealed high general health-awareness. During pregnancy, a considerable proportion of the women adapted their diet and seemed to refrain from using pain killers and from consuming alcohol, tobacco and illicit drugs. However, since a fairly large minority of the pregnant women mentioned drinking alcohol and/or smoking tobacco, further preventive work is needed.

Organic food consumption during pregnancy is associated with different consumer profiles, food patterns and intake: the KOALA Birth Cohort Study.

OBJECTIVE: To find out how the consumption of organic food during pregnancy is associated with consumer characteristics, dietary patterns and macro- and micronutrient intakes. DESIGN: Cross-sectional description of consumer characteristics, dietary patterns and macro- and micronutrient intakes associated with consumption of organic food during pregnancy. SETTING: Healthy, pregnant women recruited to a prospective cohort study at midwives' practices in the southern part of the Netherlands; to enrich the study with participants adhering to alternative lifestyles, pregnant women were recruited through various specific channels. SUBJECTS: Participants who filled in questionnaires on food frequency in gestational week 34 (n 2786). Participant groups were defined based on the share of organic products within various food types. RESULTS: Consumers of organic food more often adhere to specific lifestyle rules, such as vegetarianism or anthroposophy, than do participants who consume conventional food only (reference group). Consumption of organic food is associated with food patterns comprising more products of vegetable origin (soya/vegetarian products, vegetables, cereal products, bread, fruits, and legumes) and fewer animal products (milk and meat), sugar and potatoes than consumed in conventional diets. These differences translate into distinct intakes of macro- and micronutrients, including higher retinol, carotene, tocopherol and folate intakes, lower intakes of vitamin D and B12 and specific types of trans-fatty acids in the organic groups. These differences are seen even in groups with low consumption of organic food. CONCLUSIONS: Various consumer characteristics, specific dietary patterns and types of food intake are associated with the consumption of organic food during pregnancy.